Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice

Abstract

The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies that include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34⁺ selection and post-transplantation cyclophosphamide with tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of chronic GVHD relapse-free survival among the 3 approaches. The trial did not demonstrate a superior approach compared with Tac/MTX; however, it did highlight several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real-world practices. Here we review the results of BMT CTN 1301 and their implications for clinical practice and future clinical trial design.

Keywords: Allogeneic hematopoietic cell transplantation; CD34(+) selection; Graft-versus-host disease; Post-transplantation cyclophosphamide.

Figure 1:

Overview of the development of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) clinical trials investigating novel GVHD prevention approaches from 2011-2021. [CIBMTR- Center for International Blood and Marrow Transplant Research; HLA- human leukocyte antigen; Tac- tacrolimus; MTX- methotrexate; PTCy- post-transplant cyclophosphamide; MMF- mycophenolate mofetil; PBSC- peripheral blood stem cell; BM- bone marrow; GRFS- GVHD-free, relapse-free survival; CRFS- Chronic GVHD, relapse-free survival; HR-hazard ratio; CI- confidence interval]